The long term goal of this project is to understand the structural basis for the specificity of interactions among blood COAGULATION proteases, their inhibitors and their cofactors. Molecular details including water permable pockets and surface hydration will be computed analytically at atomic resolution using alpha shape based methods and available x-ray structures. Water transfer during functional interactions will be measured by osmotic stress technique using inert co-solutes excluded from water-permeable spaces and hydration layer of the proteins. Specifically, the aims of the proposal are: 1. Determination of the structural basis for the binding and activation of antithrombin by heparin and other glycosaminoglycans. 2. Analysis of protein-water interaction at the reactive loop and loop insertion regions of antithrombin during interaction with reactive loop peptides and glycosaminoglicans. 3. Characterization of hydration structure of tissue factor and tissue factor/factor VIIa complexes and its relationship to functional binding interaction. Analysis of structure/function relationship and water transfer during these interactions will evaluate the functional relevance of conformers in x-ray structures and will identify shape motifs of specific binding sites. This information will serve to develop therapies to prevent and control thromboembolic complications of cardiovascular disease.